POS1441 INFLUENCE OF ENVIRONMENTAL AND GENETIC FACTORS ON SERUM IGG4 DURING HEALTH CHECKUPS IN NAGASAKI ISLAND STUDY
Authors: Y. Tsuji, M. Tamai, T. Koga, S. Morimoto, S. Y. Kawashiri, F. Nonaka, H. Yamanashi, K. Arima, K. Aoyagi, T. Maeda, F. Matsuda, A. Kawakami
Journal: Annals of the Rheumatic Diseases (2022)

Background Although serum IgG4 levels are important for the diagnosis of IgG4-related diseases (IgG4-RD), few studies have validated IgG4 levels in healthy individuals in large resident medical examination cohorts and investigated background factors associated with serum IgG4. A report on genetic factors shows that HLA loci associate with IgG4-RD found in Japanese nation-wide IgG4-RD registry 1) . However, environmental and genetic factors related to the elevated serum IgG4 levels, which may closely associate with development of IgG4-RD, have previously been unclear in healthy subjects. The nephelometric immunoassay (NIA) is conventionally used to measure IgG4, but it requires a relatively large amount of serum. The magnetic bead panel assay (MBA), which can evaluate IgG4 levels with only a few ml of serum, has an advantage compared with NIA regarding to required sample volume, but the correlation between the two methods is unclear. Objectives First, we attempted to verify the accuracy of the MBA compared to the standard NIA in the first cohort. Next, we examined the relationship between IgG4 measured by the MBA and background information of healthy subjects to identify variables that correlate with serum IgG4 in the second cohort. Methods First, Kanazawa University collected 947 samples from the resident health examination, and IgG4 levels were measured by both MBA and NIA, and the correlation between the two was verified using Spearman’s rank correlation coefficient (first cohort). Next (second cohort), serum IgG4 of 3240 samples of Nagasaki Island Study (NaIS), which had started in 2014 collaborating among Nagasaki University and Goto City, Nagasaki Prefecture, intended for research of varying conditions and diseases including IgG4-RD, were then measured by MBA. These subjects were stratified into the two groups as IgG4-high and IgG4-within normal limit using the aforementioned cutoff values, and compared with background information such as age, gender, drinking, smoking, uric acid, serum creatinine, comorbidities and HLA typing, including DRB1*04:06, *04:03, *04:05, *04:10 as disease-susceptibility gene, DRB1*09:01 and DQB1*03:03 as protective gene 1) . Results IgG4 by MBA correlated well with IgG4 by NIA (r=0.94, p-value&lt;0.001) which was determined from Kanazawa samples (N=947). 1,463.6 mg/mL of IgG4 of MBA corresponded to 135 mg/dl, the normal cut-off value for IgG4 by NIA. In the analysis of NaIS samples (N=3240), the overall high IgG4 positivity rate was 6.3%. Multivariable analysis including age, gender, smoking and drinking, led by univariate analysis, showed that gender and smoking were significantly associated with high serum IgG4 positivity (male: odds ratio = 1.8, 95%CI =1.2-2.7, p = 0.009, smoking: odds ratio = 1.7, 95%CI =1.1-2.5, p = 0.012). There was no association between high serum IgG4 level and HLA genotyping. Conclusion We concluded that MBA is a good method to measure serum IgG4 even by the very small sample volume. In our study, the prevalence of serum IgG4 positivity was high tendency than previous report 2) . Our data showed that male and smoking are independent factors associated with high serum IgG4 positivity. There were no association between serum IgG4 level and HLA genotyping in healthy subjects. Further comprehensive investigation is necessary to clarify high risk subjects who will develop IgG4-RD. References [1]Terao C, et al. Lancet Rheumatol 2019;1: e14–22. [2]Carballo I, et al. PLoS One. 2016;11: e0149330. Disclosure of Interests None declared